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BACKGROUND: Approximately 25% of patients with inflammatory bowel disease (IBD) discontinue azathioprine (AZA) or mercaptopurine (MP) therapy within 3 months of treatment initiation due to adverse drug reactions. Of these side-effects, about half are due to hepatotoxicity.The aim of this study was to validate and (subsequently) optimize a previously reported predictive algorithm for thiopurine-associated hepatotoxicity by increasing the number of patients with IBD benefitting from conventional thiopurine therapy.METHODS: This multicenter observational study included consecutive thiopurine-naive patients with IBD who received AZA or MP treatment. The primary outcome was hepatotoxicity within 12 weeks. The patients with and without hepatotoxicity were compared. Four determinants, namely, age, sex, body mass index (BMI), and 6-methylmercaptopurine ribonucleotide (6-MMPR) concentrations 1 week after treatment initiation (T = 1) were used to validate and optimize two (one dichotomous and one continuous) algorithms using multivariable logistic regression analysis.RESULTS: Of 229 patients, 21 (9%) developed hepatotoxicity and 93% of the patients received MP with a median dose of 0.7 mg/kg (95% CI 0.3-1.4 mg/kg). A difference in BMI was found between with and without hepatotoxicity groups (median 27.6 versus 24.2, p = 0.022). Specificities of 68% (Algorithm 1) and 77% (Algorithm 2) and sensitivities of 56% (Algorithm 1) and 50% (Algorithm 2) were obtained.CONCLUSION: Both algorithms demonstrated limited predictive accuracy for thiopurine-induced hepatotoxicity in the validation cohort. Relevant factors contributing to this outcome were changes in thiopurine prescription behavior over time, with more MP prescriptions at relatively lower dosages of MP.

Background and Aims Paediatric inflammatory bowel disease [IBD] is characterized by altered immunological and metabolic pathways. Metabolomics may therefore increase pathophysiological understanding and could develop into characterization of biomarkers for diagnosis and IBD treatment response. However, no uniform metabolomic profiles have been identified to date. This systematic review aimed to identify faecal metabolomic signatures in paediatric IBD vs controls, and to describe metabolites associated with disease activity and treatment response. Methods A literature search was performed in Embase, Medline, Web of Science and Cochrane Library. Studies assessing faecal metabolomics in paediatric patients < 18 years with IBD [de novo, active, inactive] with comparative groups [IBD vs non-IBD; responders vs non-responders] were included. The quality of included studies was assessed according to the Newcastle–Ottawa Scale. Results Nineteen studies were included [540 patients with IBD, 386 controls], assessing faecal short-chain fatty acids [SCFA] [five studies], amino acids [AA] [ten studies], bile acids [BA] [eight studies] and other metabolites [nine studies] using various methodologies. Significantly increased levels of AA [particularly phenylalanine], primary BA and lower levels of secondary BA were described in paediatric IBD compared to controls. Faecal SCFA results varied across studies. Additionally, responders and non-responders to exclusive enteral nutrition and infliximab showed differences in baseline faecal metabolites [based on BA, AA]. Conclusions This systematic review provides evidence for distinct faecal metabolomic profiles in paediatric IBD. However, results varied across studies, possibly due to differences in study design and applied analytical techniques. Faecal metabolomics could provide more insight into host–microbial interactions in IBD, but further studies with standardized methodologies and reporting are needed.

Contains fulltext : 290620.pdf (Publisher’s version ) (Open Access) BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. AIM: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. METHODS: Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate. RESULTS: We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. CONCLUSION: Tofacitinib was effective in 31.8% of patients after 24 months of treatment. 01 januari 2023

Background Fecal metabolomic profiles differ between pediatric inflammatory bowel disease (IBD) patients and controls and may provide new insights in the pathophysiology of IBD. The role of amino acids, however, is not fully elucidated. We aimed to assess fecal amino acid profiles in pediatric IBD. Methods In this case-control study, treatment-naïve, newly diagnosed pediatric IBD patients and a non-IBD control group, matched based on sex and age, were included in 2 tertiary centres. Fecal amino acid profiles were assessed using a targeted high-performance liquid chromatography technique. A random forest classifier method was used to develop a prediction model differentiating IBD from controls and predicting IBD phenotype. The association between IBD localization and amino acid concentrations was tested with ordinal regression models. Results We included 78 newly diagnosed IBD patients (40 Crohn’s disease [CD], 38 ulcerative colitis [UC]) and 105 controls. Patients with IBD could be differentiated from controls with an accuracy of 82% (sensitivity 63%, specificity 97%). Twenty-nine out of the 42 measured unique amino acids were included in the prediction model. Increased levels of tryptophan, taurine, alanine, ornithine, valine, histidine, and leucine were the most differentiating features. Children with CD and UC could be differentiated from the controls with an accuracy of 80% and 90%, respectively. Inflammatory bowel disease phenotype could not be predicted. Tryptophan, valine, and histidine levels were positively associated with more extended disease in UC patients (P < .05). Conclusions Fecal amino acids may enhance understanding of the role of host-microbial interactions in the pathophysiology of IBD and may evolve into biomarkers for pediatric IBD diagnostic and personalized medicine.

BackgroundOrofacial granulomatosis [OFG] is a rare syndrome that may be associated with Crohn’s disease [CD]. We aimed to characterise this relationship and the management options in the biologic era.MethodsThis multicentre case series was supported by the European Crohn’s and Colitis Organisation [ECCO], and performed as part of the Collaborative Network of Exceptionally Rare case reports [CONFER] project. Clinical data were recorded in a standardised collection form.ResultsThis report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 standard deviation [SD]) and 14 females [40.3 years, ±21.0 SD]. Non-oral upper gastrointestinal tract involvement was seen in six cases and perianal disease in 11. The diagnosis of OFG was made before CD diagnosis in two patients, concurrently in eight, and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in six. Remission was achieved in 23 patients, notably with the use of anti-tumour necrosis factors [TNFs] in nine patients, vedolizumab in one, ustekinumab in one, and thalidomide in two. A further five cases were resistant to therapies including anti-TNFs.ConclusionsOFG associated with CD may occur before, concurrently with, or after the diagnosis of CD. Perianal and upper gastrointestinal [UGI] disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several biologics approved for CD.

OBJECTIVE: Inflammatory bowel disease (IBD) patients experience problems at work resulting in work productivity loss driving indirect healthcare costs. We aimed to find determinants for work productivity loss in employed IBD patients while correcting for disease severity according to prior and active maintenance treatment. METHODS: In this longitudinal multicentre cohort study, 510 employed IBD patients completed online questionnaires during 18 months follow-up. Work productivity, fatigue and health-related quality of life (HRQL) were measured using the Work Productivity and Activity Impairment questionnaire, the Multidimensional Fatigue Inventory (score 20-100) and Short-Inflammatory Bowel Disease Questionnaire (score 10-70). Linear mixed model analyses including random, repeated and fixed effects were performed. RESULTS: Fatigue (β 0.22; 95% CI, 0.12-0.32) and reduced HRQL (β -1.15; 95% CI, -1.35 to -0.95) were the strongest determinants for work productivity loss in employed IBD patients. Clinical disease activity (β 9.50, 95% CI 6.48-12.51) and corticosteroid use (β 10.09, 95% CI 5.25-15.84) were associated with work productivity loss in the total IBD group and ulcerative colitis subgroup, but not in Crohn's disease patients. History of IBD-related surgery (β 9.41; 95% CI, 2.62-16.20) and vedolizumab use (β 12.74; 95% CI, 3.63-21.86) were significantly associated with work productivity loss in the ulcerative colitis subgroup. CONCLUSIONS: Fatigue and reduced HRQL were the strongest determinants for work productivity loss in employed IBD patients while correcting for disease severity and activity. These results underline the importance of monitoring fatigue and HRQL in routine care to reduce work productivity loss and indirect costs.

Contains fulltext : 238426.pdf (Publisher’s version ) (Open Access) BACKGROUND: Work-related aspects are important determinants of health for inflammatory bowel disease (IBD) patients. AIMS: We aimed to describe quality of working life (QWL) in IBD patients and to assess variables that are associated with QWL. METHODS: Employed IBD patients of two tertiary and two secondary referral hospitals were included. QWL (range 0-100) was measured using the Quality of Working Life Questionnaire (QWLQ). Work productivity (WP), fatigue, and health-related quality of life (HRQL) were assessed using the Work Productivity and Activity Impairment questionnaire, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire, respectively. Active disease was defined as a score > 4 for the patient-reported Harvey-Bradshaw index in Crohn's disease (CD) or Simple Clinical Colitis Activity Index in ulcerative colitis patients. RESULTS: In total, 510 IBD patients were included (59% female, 53% CD, mean age 43 (SD 12) years). The mean QWLQ score was 78 (SD 11). The lowest subscore (54 (SD 26)) was observed for "problems due to the health situation": 63% reported fatigue-related problems at work, 48% agreed being hampered at work, 46% had limited confidence in their body, and 48% felt insecure about the future due to their health situation. Intermediate/strong associations were found between QWL and fatigue (r = - 0.543, p

Thiopurines (mercaptopurine, azathioprine and thioguanine) are well-established maintenance treatments for a wide range of diseases such as leukemia, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and other inflammatory and autoimmune diseases in general. Worldwide, millions of patients are treated with thiopurines. The use of thiopurines has been limited because of off-target effects such as myelotoxicity and hepatotoxicity. Therefore, seeking methods to enhance target-based thiopurine-based treatment is relevant, combined with pharmacogenetic testing. Controlled-release formulations for thiopurines have been clinically tested and have shown promising outcomes in inflammatory bowel disease. Latest developments in nano-formulations for thiopurines have shown encouraging pre-clinical results, but further research and development are needed. This review provides an overview of novel drug delivery strategies for thiopurines, reviewing modified release formulations and with a focus on nano-based formulations.

Objectives Although bowel symptoms are often predominant, inflammatory bowel disease (IBD) patients can have several oral manifestations. The aim of this study was to investigate the prevalence of dental caries and periodontal disease in patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to an age and gender-matched control group of patients without IBD. Material and methods The DMFT (Decayed, Missing, Filled Teeth) scores and the DPSI (Dutch Periodontal Screening Index) of 229 IBD patients were retrieved from the electronic health record patient database axiUm at the Academic Centre for Dentistry Amsterdam (ACTA) and were compared to the DMFT scores and DPSI from age and gender-matched non-IBD patients from the same database. Results The total DMFT index was significantly higher in the IBD group compared to the control group. When CD and UC were analyzed separately, a statistically significant increased DMFT index was observed in CD patients but not in UC patients. The DPSI did not differ significantly between the IBD and non-IBD groups for each of the sextants. However, in every sextant, IBD patients were more frequently edentulous compared to the control patients. Conclusion CD patients have significantly more dental health problems compared to a control group. Periodontal disease did not differ significantly between IBD and non-IBD groups as determined by the DPSI. Clinical relevance It is important that IBD patients and physicians are instructed about the correlation between their disease and oral health problems. Strict oral hygiene and preventive dental care such as more frequent checkups should be emphasized by dental clinicians.

Thioguanine (TG) has been shown as a safe alternative in adults with inflammatory bowel disease (IBD) who did not tolerate conventional thiopurines [azathioprine (AZA)/mercaptopurine]. However, data in pediatric IBD are scarce. Therefore, we aimed to assess the safety of TG as maintenance therapy.A retrospective, multicenter cohort study of children with IBD on TG was performed in the Netherlands. TG-related adverse events (AE) were assessed and listed according to the common terminology criteria for AE.Thirty-six children with IBD (median age 14.5 years) on TG (median dose 15 mg/day) were included in 6 centers. Five AE occurred during follow-up [pancreatitis (grade 3), hepatotoxicity (grade 3) (n = 2), Clostridium difficile infection (grade 2), and abdominal pain (grade 2)]. All patients (n = 8) with a previously AZA-induced pancreatitis did not redevelop pancreatitis on TG.In pediatric IBD, TG seems a safe alternative in case of AZA-induced pancreatitis. Further research assessing long-term TG-related safety and efficacy is needed.

ObjectiveRevised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants.DesignIn this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing.ResultsCompared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points.ConclusionWe confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health.

Background The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. Methods This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). Results Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. Conclusions Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker.

Summary Background: The role of esophageal microbiota in esophageal cancer treatment is gaining renewed interest, largely driven by novel DNA-based microbiota analysis techniques. The aim of this systematic review is to provide an overview of current literature on the possible association between esophageal microbiota and outcome of esophageal cancer treatment, including tumor response to (neo)adjuvant chemo(radio)therapy, short-term surgery-related complications, and long-term oncological outcome. Methods: A systematic review of literature was performed, bibliographic databases were searched and relevant articles were selected by two independent researchers. The Newcastle-Ottawa scale was used to estimate the quality of included studies. Results: The search yielded 1303 articles, after selection and cross-referencing, five articles were included for qualitative synthesis and four studies were considered of good quality. Two articles addressed tumor response to neoadjuvant chemotherapy and described a correlation between high intratumoral Fusobacterium nucleatum levels and a poor response. One study assessed surgery-related complications, in which no direct association between esophageal microbiota and occurrence of complications was observed. Three studies described a correlation between shortened survival and high levels of intratumoral F. nucleatum, a low abundance of Proteobacteria and high abundances of Prevotella and Streptococcus species. Conclusions: Current evidence points towards an association between esophageal microbiota and outcome of esophageal cancer treatment and justifies further research. Whether screening of the individual esophageal microbiota can be used to identify and select patients with a predisposition for adverse outcome needs to be further investigated. This could lead to the development of microbiota-based interventions to optimize esophageal microbiota composition, thereby improving outcome of patients with esophageal cancer.

Background The Crohn’s disease (CD) phenotype differs between Asian and Western countries and may affect disease management, including decisions on surgery. This study aimed to compare the indications, postoperative management, and long-term prognosis after ileocecal resection (ICR) in Hong Kong (HK) and the Netherlands (NL). Methods CD patients with primary ICR between 2000 and 2019 were included. The endpoints were endoscopic (Rutgeerts score ≥i2b and/or radiologic recurrence), clinical (start or switch of inflammatory bowel disease medication), and surgical recurrences. Cumulative incidences of recurrence were estimated with a Bayesian multivariable proportional hazards model. Results Eighty HK and 822 NL patients were included. The most common indication for ICR was penetrating disease (HK: 32.5%, NL: 22.5%) in HK vs stricturing disease (HK: 32.5%, NL: 48.8%) in the NL (P < .001). Postoperative prophylaxis was prescribed to 65 (81.3%) HK patients (28 [35.0%] aminosalicylates [5-aminosalicylic acid]; 30 [37.5%] immunomodulators; 0 biologicals) vs 388 (47.1%) NL patients (67 [8.2%] 5-aminosalicylic acid; 187 [22.8%] immunomodulators; 69 [8.4%] biologicals; 50 [6.1%] combination therapy) (P < .001). Endoscopic or radiologic evaluation within 18 months was performed in 36.3% HK vs 64.1% NL (P < .001) patients. No differences between both populations were observed for endoscopic (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.21), clinical (HR, 0.91; 95% CI, 0.62-1.32), or surgical (HR, 0.61; 95% CI, 0.31-1.13) recurrence risks. Conclusion The main indication for ICR in CD patients is penetrating disease in HK patients and stricturing disease in NL patients. Although considerable pre- and postoperative management differences were observed between the two geographical areas, the long-term prognosis after ICR is similar.

Aims Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin [IL]-12 and IL-23. It is registered for the treatment of inflammatory bowel diseases. We assessed the 2-year effectiveness and safety of ustekinumab in a real world, prospective cohort of patients with Crohn’s disease [CD]. Methods Patients who started ustekinumab were prospectively enrolled in the nationwide Initiative on Crohn and Colitis [ICC] Registry. At weeks 0, 12, 24, 52 and 104, clinical remission Harvey Bradshaw Index≤ 4 points], biochemical remission (faecal calprotectin ≤ 200 μg/g and/or C-reactive protein ≤5 mg/L], perianal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission at week 104. Results In total, 252 CD patients with at least 2 years of follow-up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission was 32.3% [81/251], 41.4% [104/251], 39% [97/249] and 34.0% [84/247] at weeks 12, 24, 52 and 104, respectively. In patients with combined clinical and biochemical disease activity at baseline [n = 122], the corticosteroid-free clinical remission rates were 23.8% [29/122], 35.2% [43/122], 40.0% [48/120] and 32.8% [39/119] at weeks 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks in all patients was 64.3% and 54.8%, respectively. The main reason for discontinuing treatment after 52 weeks was loss of response [66.7%]. No new safety issues were observed. Conclusion After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission.

Background Work productivity (WP) loss includes absence from work (absenteeism) and productivity loss while working (presenteeism), which leads to high indirect costs in inflammatory bowel disease (IBD). Prior health economic analyses predominantly focused on absenteeism. Here we focus on presenteeism and assess predictors of WP loss, fatigue, and reduced health-related quality of life (HRQL). Methods Employed IBD patients completed the following surveys: Work Productivity and Activity Impairment, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire. Predictors were assessed using uni- and multivariable regression analyses. Annual costs were calculated using percentages of WP loss, hourly wages, and contract hours. Results Out of 1590 invited patients, 768 (48%) responded and 510 (32%) were included. Absenteeism, presenteeism, and overall WP loss were reported by 94 (18%), 257 (50%), and 269 (53%) patients, respectively, resulting in mean (SD) annual costs of €1738 (5505), €5478 (8629), and €6597 (9987), respectively. Disease activity and active perianal disease were predictors of WP loss (odds ratio [OR] = 6.6; 95% confidence interval [CI], 3.6-12.1); OR = 3.7; 95% CI, 1.5-8.7). Disease activity and arthralgia were associated with fatigue (OR = 3.6; 95% CI, 1.9-6.8; OR = 1.8; 95% CI, 1.0-3.3)) and reduced HRQL (OR = 10.3; 95% CI, 5.9-17.9; OR = 2.3; 95 % CI, 1.4-3.8). Fatigue was the main reason for absenteeism (56%) and presenteeism (70%). Fatigue and reduced HRQL led to increased costs compared with absence of fatigue and normal HRQL (mean difference = €6630; 95% CI, €4977–€8283, P < 0.01; mean difference = €9575; 95% CI, €7767–€11,384, P < 0.01). Conclusions Disease activity and disease burden lead to WP loss in approximately half of the employed IBD population, driving indirect costs. Fatigue is the most important reason for WP loss.

Necrotizing enterocolitis (NEC) is one of the most common and lethal gastrointestinal diseases in preterm infants. Early recognition of infants in need for surgical intervention might enable early intervention. In this multicenter case-control study, performed in nine neonatal intensive care units, preterm born infants (< 30 weeks of gestation) diagnosed with NEC (stage ≥ IIA) between October 2014 and August 2017 were divided into two groups: (1) medical (conservative treatment) and (2) surgical NEC (sNEC). Perinatal, clinical, and laboratory parameters were collected daily up to clinical onset of NEC. Univariate and multivariate logistic regression analyses were applied to identify potential predictors for sNEC. In total, 73 preterm infants with NEC (41 surgical and 32 medical NEC) were included. A low gestational age (p value, adjusted odds ratio [95%CI]; 0.001, 0.91 [0.86–0.96]), no maternal corticosteroid administration (0.025, 0.19 [0.04–0.82]), early onset of NEC (0.003, 0.85 [0.77–0.95]), low serum bicarbonate (0.009, 0.85 [0.76–0.96]), and a hemodynamically significant patent ductus arteriosus for which ibuprofen was administered (0.003, 7.60 [2.03–28.47]) were identified as independent risk factors for sNEC.Conclusions: Our findings may support the clinician to identify infants with increased risk for sNEC, which may facilitate early decisive management and consequently could result in improved prognosis. What is Known:• In 27–52% of the infants with NEC, a surgical intervention is indicated during its disease course.• Absolute indication for surgical intervention is bowel perforation, whereas fixed bowel loop or clinical deterioration highly suggestive of bowel perforation or necrosi, is a relative indication. What is New:• Lower gestational age, early clinical onset, and no maternal corticosteroids administration are predictors for surgical NEC.• Low serum bicarbonate in the 3 days prior clinical onset and patent ductus arteriosus for which ibuprofen was administered predict surgical NEC.

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics’ effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age 72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19–0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35–0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85–0.97]; p = 0.003).Conclusion: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored. What is Known:• Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis.• The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated. What is New:• Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged.• A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life.

Surgical construction of a vagina may be indicated in transgender women and cisgender women with congenital or acquired vaginal absence. It has a positive effect on quality of life and generally en...

BACKGROUND: The LIR!C trial showed that laparoscopic ileocaecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with infliximab, an anti-tumour necrosis factor (TNF) drug. We aimed to compare long-term outcomes of both interventions and identify baseline factors associated with the duration of treatment effect in each group.METHODS: In this retrospective follow-up study, we collected data from patients who participated in the LIR!C trial, a multicentre randomised controlled trial that compared quality of life after surgical resection versus infliximab in adult patients with non-stricturing and immunomodulator-refractory ileocaecal Crohn's disease. From Jan 1 to May 1, 2018, we collected follow-up data from the time from enrolment in the LIR!C trial until the last visit at either the gastrointestinal surgeon or gastroenterologist. In this study, outcomes of interest were need for surgery or repeat surgery or anti-TNF therapy, duration of treatment effect, and identification of factors associated with the duration of treatment effect. Duration of treatment effect was defined as the time without need for additional Crohn's disease-related treatment (corticosteroids, immunomodulators, biologics, or surgery).FINDINGS: We collected long-term follow-up data for 134 (94%) of 143 patients included in the LIR!C trial, of whom 69 were in the resection group and 65 were in the infliximab group. Median follow-up was 63·5 months (IQR 39·0-94·5). In the resection group, 18 (26%) of 69 patients started anti-TNF therapy and none required a second resection. 29 (42%) patients in the resection group did not require additional Crohn's disease-related medication, although 14 (48%) of these patients were given prophylactic immunomodulator therapy. In the infliximab group, 31 (48%) of 65 patients had a Crohn's disease-related resection, and the remaining 34 patients maintained, switched, or escalated their anti-TNF therapy. Duration of treatment effect was similar in both groups, with a median time without additional Crohn's disease-related treatment of 33·0 months (95% CI 15·1-50·9) in the resection group and 34·0 months (0·0-69·3) in the infliximab group (log-rank p=0·52). In both groups, therapy with an immunomodulator, in addition to the allocated treatment, was associated with duration of treatment effect (hazard ratio for resection group 0·34 [95% CI 0·16-0·69] and for infliximab group 0·49 [0·26-0·93]).INTERPRETATION: These findings further support laparoscopic ileocaecal resection as a treatment option in patients with Crohn's disease with limited (affected segment ≤40 cm) and predominantly inflammatory terminal ileitis for whom conventional treatment is not successful.FUNDING: None.

Background: Since the start of the COVID-19 pandemic, there have been many scientific reports regarding gastrointestinal manifestations. Several reports indicate the possibility of viral shedding via faeces and the possibility of faecal-oral transmission. Aims: To critically assess the clinical relevance of testing stool samples and anal swabs and provide an overview of the potential faecal-oral transmission of SARS-CoV-2. Methods: A systematic literature search with MeSH terms was performed, scrutinising the Embase database, Google scholar, MEDLINE database through PubMed and The Cochrane Library, including articles from December 2019 until July 7 2020. Data were subsequently analysed with descriptive statistics. Results: Ninety-five studies were included in the qualitative analysis. 934/2149 (43%) patients tested positive for SARS-CoV-2 in stool samples or anal swabs, with positive test results up to 70 days after symptom onset. A meta-analysis executed with studies of at least 10 patients revealed a pooled positive proportion of 51.8% (95% CI 43.8 - 59.7%). Positive faecal samples of 282/443 patients (64%) remained positive for SARS-CoV-2 for a mean of 12.5 days, up to 33 days maximum, after respiratory samples became negative for SARS-CoV-2. Viable SARS-CoV-2 was found in 6/17 (35%) patients in whom this was specifically investigated. Conclusions: Viral shedding of SARS-CoV-2 in stool samples occurs in a substantial proportion of patients, making faecal-oral transmission plausible. Furthermore, detection in stool samples or anal swabs can persist long after negative respiratory testing. Therefore, stool sample or anal swab testing should be (re)considered in relation to decisions for isolating or discharging a patient.

BACKGROUND: Although ulcerative colitis primarily involves the colon, extra-intestinal manifestations are common and oral and dental complaints are no exception.OBJECTIVE: This study aims at evaluating oral and dental health problems and salivary function and composition in ulcerative colitis patients and its correlation with disease activity.METHODS: Xerostomia Inventory score, (unstimulated/stimulated) salivary flow rates, salivary amylase and mucin/ Mucin 5B levels, self-reported oral and dental complaints, the oral health related quality of life, Simple Clinical Colitis Activity Index and inflammatory bowel disease-specific health related quality of life were determined.RESULTS: The cohort consisted of 51 ulcerative colitis patients. Hyposalivation was experienced by 16% of patients under resting conditions and 24% under chewing-stimulated conditions. Xerostomia was not correlated with salivary flow rates. Disease activity did not influence salivary amylase and Mucin 5B concentrations. The Xerostomia Inventory score was correlated with the Simple Clinical Colitis Activity Index (p = 0.042) and inflammatory bowel disease-specific health related quality of life (p = 0.001). Most reported oral health problems were halitosis (29%) and aphthae (28%). Frequently reported dental problems were cavities (35%) and gum problems (31%). Patients with active disease experienced significantly more oral and dental complaints. The number of oral problems was positively correlated with the Simple Clinical Colitis Activity Index (p = 0.045) and negatively correlated with the inflammatory bowel disease-specific health related quality of life (p = 0.005).CONCLUSION: The subjective feeling of a dry mouth (xerostomia) is related to disease activity and disease activity-associated quality of life in ulcerative colitis patients, whereas the objective saliva secretion rate is not. Oral and dental health problems are frequently observed in patients with ulcerative colitis, especially during active disease.

Background Patients with inflammatory bowel disease (IBD) express a need for additional psychotherapy; however, psychological support is not incorporated in the routine care of persons with IBD. This systematic review aims to assess the effect of psychotherapy on quality of life (QoL). Methods A systematic search was conducted on October 7, 2019, using Embase, Medline (Ovid), PubMed, Cochrane, Web of Science, PsycInfo, and Google Scholar to collect all types of clinical trials with psychotherapeutic interventions that measured QoL in patients with IBD aged ≥18 years. Quality of evidence was systematically assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria. Results Out of 2560 articles, 31 studies (32 articles) were included with a total number of 2397 patients with active and inactive IBD. Of the 31 eligible studies, 11 reported a significant positive effect and 6 had ambiguous results regarding the impact of psychotherapeutic interventions on QoL. Treatment modalities differed in the reported studies and consisted of cognitive-behavioral therapy, psychodynamic therapy, acceptance and commitment therapy, stress management programs, mindfulness, hypnosis, or solution-focused therapy. All 4 studies focusing on patients with active disease reported a positive effect of psychotherapy. Trials applying cognitive-behavioral therapy reported the most consistent positive results. Conclusions Psychotherapeutic interventions can improve QoL in patients with IBD. More high-quality research is needed before psychological therapy may be implemented in daily IBD practice and to evaluate whether early psychological intervention after diagnosis will result in better coping strategies and QoL throughout life.

Inflammatory bowel disease (IBD) is diagnosed and monitored using endoscopic assessment, which is invasive and costly. In this study, potential of faecal volatile organic compounds (VOC) analysis for IBD detection and identification of disease activity was evaluated.IBD patients visiting outpatient clinics of participating tertiary hospitals were included. Active disease was defined as FCP ≥250 mg/g, remission as FCP

Background: Inflammatory Bowel Disease (IBD) can have considerable effects on employment outcomes because of its disabling character. Goals: We aimed to investigate the impact of IBD in the workplace and to better understand the need for accommodations and adaptations. Study: Between November 2017 and March 2018, IBD patients were recruited from outpatient clinics in Christchurch Hospital, New Zealand. The survey assessed employment, the need for workplace accommodations and the difficulty arranging it, insurance, and disability using the item-reduced Inflammatory Bowel Disease Disability Index for self-report (IBD-DI-SR). Data were analyzed using descriptive statistics and multivariate logistic regression modeling. Results: One hundred twenty-three patients were included (response rate 64%), 112 of whom reported that they experienced symptoms while working (60% female, 71% Crohn’s disease, mean age 41.9 years). Ninety-one percent needed at least 1 workplace accommodation when symptoms were most severe. Almost half of the patients who needed an accommodation had difficulty arranging it. The most needed accommodations were time to go to medical appointments (71%) and easy access to a suitable toilet (71%). Being female, having less effective medication, and being distressed were associated with the need for 2 or more accommodations, difficulty in arranging accommodations, and not asking for needed accommodation. Conclusions: Many IBD patients need accommodations at work while symptomatic in order to overcome workplace disability, which can be difficult to arrange. Improved resources are needed to inform employees and employers about the disease, the possibilities for workplace accommodations, and practical strategies to request them.

In this prospective intention-to-diagnose pilot study, we aimed to assess accuracy of serum and fecal amino-acids to discriminate de novo pediatric inflammatory bowel disease (IBD) and non-IBD children. Patients with suspected IBD were allocated the IBD (n = 11) or non-IBD group (n = 8) following laboratory testing or endoscopy according to the revised Porto-criteria. Fecal calprotectin levels were obtained, an additional blood and fecal sample were collected. Fecal and serum amino-acid profiles were analyzed using high performance-liquid chromatography. Nine fecal amino-acids (alanine [area under the curve 0.94], citrulline [0.94], glutamine [0.89], leucine [0.98], lysine [0.89], phenylalanine [0.99], serine [0.91], tyrosine [0.96], and valine [0.95]) differed significantly between IBD and non-IBD. In serum, no significant differences were observed. This study underlines the potential of fecal amino-acids as novel, adjuvant noninvasive, and low-cost biomarkers in the diagnostic work-up of pediatric IBD detection.

BACKGROUND: Individuals with Lynch syndrome are at high risk for colorectal cancer (CRC). Regular colonoscopies have proven to decrease CRC incidence and mortality. However, colonoscopy is burdensome and interval CRCs still occur. Hence, an accurate, less-invasive screening method that guides the timing of colonoscopy would be of important value.AIM: To outline the performance of non-endoscopic screening modalities for Lynch-associated CRC and adenomas.METHODS: Systematic literature search in MEDLINE and EMBASE to identify studies investigating imaging techniques and biomarkers for detection of CRC and adenomas in Lynch syndrome. The QUADAS-2 tool was used for the quality assessment of included studies.RESULTS: Seven of 1332 screened articles fulfilled the inclusion criteria. Two studies evaluated either CT colonography or MR colonography; both techniques were unable to detect CRC and (advanced) adenomas CONCLUSIONS: Imaging techniques are unsuitable for colon surveillance in Lynch syndrome, whereas biomarkers are understudied. Having outlined biomarker research in Lynch-associated and sporadic CRC/adenomas, we believe that these non-invasive markers may hold potential (whether or not combined) for this population. As they could be of great value, (pre-)clinical studies in this field should be prioritised.

BACKGROUND: In the recent era of growing availability of biological agents, the role of thiopurines needs to be reassessed with the focus on toxicity. AIMS: We assessed the incidence and predictive factors of thiopurine-induced adverse events (AE) resulting in therapy cessation in pediatric inflammatory bowel disease (IBD), related to thiopurine metabolites and biochemical abnormalities, and determined overall drug survival. METHODS: We performed a retrospective, single-center study of children diagnosed with IBD between 2000 and 2019 and treated with thiopurine therapy. The incidence of AE and overall drug survival of thiopurines were evaluated using the Kaplan-Meier method. Correlations between thiopurine metabolites and biochemical tests were computed using Spearman's correlation coefficient. RESULTS: Of 391 patients with IBD, 233 patients (162 Crohn's disease, 62 ulcerative colitis, and 9 IBD-unclassified) were prescribed thiopurines (230 azathioprine and 3 mercaptopurine), of whom 50 patients (22%) discontinued treatment, at least temporary, due to thiopurine-induced AE (median follow-up 20.7 months). Twenty-six patients (52%) were rechallenged and 18 of them (70%) tolerated this. Sixteen patients (6%) switched to a second thiopurine agent after azathioprine intolerance and 10 of them (63%) tolerated this. No predictive factors for development of AE could be identified. Concentrations of 6-thioguanine nucleotides (6-TGN) were significantly correlated with white blood cell and neutrophil count, 6-methylmercaptopurine (6-MMP) concentrations with alanine aminotransferase and gamma-glutamyltranspeptidase. CONCLUSIONS: Approximately 20% of pediatric patients with IBD discontinued thiopurine treatment due to AE. A rechallenge or switch to mercaptopurine is an effective strategy after development of AE. Concentrations of 6-TGN and 6-MMP are associated with biochemical abnormalities. ispartof: DIGESTIVE DISEASES AND SCIENCES vol:67 issue:1 pages:241-251 ispartof: location:United States status: published

Background Hypogammaglobulinaemia is a disorder characterized by low serum immunoglobulin levels and a high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease [IBD]. Methods This was a multicentre case series performed as a part of the European Crohn’s and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. Results This report includes 27 patients with primary hypogammaglobulinaemia and IBD-like features: 20 males and seven females, median age 45.6 years (interquartile range [IQR] 35.2–59). Crohn’s disease-like features were noted in 23 patients, and four patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinaemia preceded a diagnosis of IBD-like features in 20 patients [median of 7 years prior, IQR 2.6–20.6 years], and followed the appearance of IBD-like features in seven cases [median of 1 year after, IQR 0.45–5.6 years]. Hypogammaglobulinaemia aetiologies were common variable immunodeficiency [66.6%], agammaglobulinaemia [7.4%], selective IgA-deficiency [11.1%], Good’s syndrome [7.4%], IgG subclass deficiency with IgA deficiency [3.7%] and hyper-IgM [3.7%]. In addition to antibiotics and intravenous immunoglobulin [IVIG] for hypogammaglobulinaemia, 12 patients received IBD-related treatment including 5-aminosalicylate agents [two patients], corticosteroids [one patient], thiopurines [three patients], anti-tumour necrosis factor [four patients] and vedolizumab [two patients]. By the end of the follow-up (44.5 months [IQR 18–81]), 21/27 [77%] patients were in clinical remission. Conclusion This case series describes IBD-like features in patients with hypogammaglobulinaemia. The diagnosis of IBD-like features mainly occurred after that of hypogammaglobulinaemia, with successful recovery in the majority of cases after appropriate treatment.

Introduction Bloodstream infections (BSIs) cause treatment-related mortality in pediatric acute leukemia. We explored the potential of intestinal microbiota and fecal volatile organic compounds (VOCs) analyses to predict BSI. Methods In this case-control study, fecal samples of pediatric acute leukemia patients were collected. Microbiota composition and fecal VOC profiles of BSI cases and matched non-BSI controls were compared. Results In total, 6 patients were included, of which 1 developed BSI and 1 neutropenic fever. Both showed reduced microbial diversity and stability of Bacteroidetes. In the BSI case, Pantoea was identified 15 days before BSI. Significant differences in fecal VOC profiles were measured between the case and controls. Conclusion Microbiota and fecal VOC could serve as biomarkers to predict BSI in pediatric leukemia.

Background Gastrointestinal diseases can have oral manifestations. The aim of this study was to investigate the knowledge of gastroenterologists and dentists about gastrointestinal diseases with oral manifestations and to assess the frequency, extent and content of communication between gastroenterologists and oral healthcare professionals. Methods Separate questionnaires were developed and sent to all 523 gastroenterologists and a random selection of 500 dentists in the Netherlands. Both questionnaires contained questions about demographic characteristics of the participants, 10 statements about gastrointestinal diseases with possible oral manifestations and questions about the communication between gastroenterologists and oral healthcare professionals. Additionally, the questionnaire for gastroenterologists contained 9 statements about general dentistry and the questionnaire for dentist had 9 questions about gastrointestinal diseases. Results Gastroenterologists answered 47.6% ± 31.9% of the questions correct about gastrointestinal diseases with possible oral manifestations and 57.5% ± 27.9% of the questions correct about general dentistry. Dentists answered 26.6% ± 20.5% of the questions correct about possible oral manifestations of gastrointestinal diseases and 50.3% ± 18.7% of the questions correct about gastrointestinal diseases. Gastroenterologists and dentists valued interdisciplinary consultation as very useful with scores of 4.07 ± 0.70 and 4.67 ± 0.49 on a 5-point Likert scale, respectively, but the frequency of consultation was considered insufficiently with a mean score of 2.88 ± 1.01 and 2.24 ± 1.05 on a 5-point Likert scale, respectively. Conclusions This study suggests that the knowledge of gastroenterologists and dentists about gastrointestinal diseases with oral manifestations could be improved. Interdisciplinary consultation was considered valuable for the optimal treatment of their patients but was assessed as insufficient.

The introduction of capsule endoscopy two decades ago marked the beginning of the “small bowel revolution”. Since then, the rapid evolution of microtechnology has allowed the development of drug delivery systems (DDS) designed to address some of the needs that are not met by standard drug delivery. To overcome the complex anatomy and physiology of the gastrointestinal (GI) tract, several DDS have been developed, including many prototypes being designed, built and eventually produced with ingenious drug-release mechanisms and anchoring systems allowing targeted therapy. This review highlights the currently available systems for drug delivery in the GI tract and discusses the needs, limitations, and future considerations of these technologies.

Background and Aims Many inflammatory bowel disease [IBD] patients in remission have persisting symptoms, compatible with irritable bowel syndrome [IBS-type symptoms]. We aimed to compare the effectiveness of gut-directed hypnotherapy vs standard medical treatment [SMT] for IBS-type symptoms in IBD patients. Methods In this multicentre, randomized, controlled, open-label trial, patients aged 12–65 years with IBD in clinical remission [global assessment] and biochemical remission [faecal calprotectin ≤100 µg/g, or ≤200 µg/g without inflammation at endoscopy] with IBS according to Rome III criteria were randomized to hypnotherapy or SMT. Primary outcome was the proportion with ≥50% reduction on a visual analog scale for symptom severity, as measured with the Irritable Bowel Syndrome Severity Scoring System [IBS-SSS] at week 40 [i.e. 6 months after finishing the intervention], compared to baseline. Secondary outcomes included total IBS-SSS score, quality of life, adequate relief, IBS-related cognitions, and depression and anxiety scores. Results Eighty patients were included, of whom 70 received at least one session of the allocated treatment and were included in the modified intention-to-treat-population. Seven patients were excluded because of missing baseline data required for the primary outcome. The primary outcome was met in nine [27%] of 33 patients randomized to SMT and nine [30%] of 30 patients randomized to hypnotherapy [p = 0.81]. Adequate relief was reported in 60% and 40% of subjects, respectively. Exploratory analyses of secondary outcomes revealed no apparent differences between the two treatment groups. Conclusions Hypnotherapy was not superior to SMT in the treatment of IBS-type symptoms in IBD patients. Both treatment strategies are reasonable options from a clinical perspective.

BACKGROUND: Low-dose thiopurine-allopurinol (LDTA) combination therapy is a commonly applied optimisation strategy in IBD patients with a skewed thiopurine metabolism.AIM: To assess continued LDTA maintenance treatment at annual intervals and explore risk factors for treatment cessation METHODS: Adult IBD patients treated with LDTA between 2009 and 2016 were retrospectively included. Data on the incidence of clinical and laboratory adverse events (AEs), including hepatotoxicity and myelotoxicity resulting in imposing LDTA therapy cessation and associated risk factors were collected.RESULTS: In total, 221 IBD patients (46% male, median age 42 years) were included. Maintenance LDTA treatment was continued in 78% of patients at 1 year (n = 145), 66% at 2 years (n = 83), 57% at 3 years (n = 52) and 52% at 4 years (n = 33). Treatment in patients receiving LDTA therapy for AEs during thiopurine monotherapy was more often continued than in patients initiating LDTA for other indications (eg, ineffectiveness of thiopurine monotherapy, routinely discovered skewed metabolism) (P = 0.016). Myelotoxicity during thiopurine monotherapy resolved in 87% and hepatotoxicity in 86% after median of 1.2 and 1.4 months after LDTA initiation. Cumulative incidence of AEs during LDTA resulting in therapy cessation within total follow-up of 449 treatment-years was 7% for clinical AEs, 4% for myelotoxicity and 1% for hepatotoxicity.CONCLUSION: LDTA therapy is a safe and beneficial optimisation strategy in IBD patients. Continued maintenance LDTA treatment is 52% after 4 years of treatment and most commonly affected by ineffectiveness of LDTA rather than LDTA-attributed toxicity. LDTA optimisation strategy is most advantageous in patients failing thiopurine monotherapy due to AEs.

Background: Thioguanine is associated with liver toxicity, especially nodular regenerative hyperplasia (NRH). We assessed if liver histology alters during long-term maintenance treatment with thioguanine in patients with inflammatory bowel disease (IBD). Methods: Liver specimens of thioguanine treated IBD patients with at least two liver biopsies were revised by two independent liver pathologists, blinded to clinical characteristics. Alterations in histopathological findings between first and sequential liver specimen were evaluated and associated clinical data, including laboratory parameters and abdominal imaging reports, were collected. Results: Twenty-five IBD patients underwent sequential liver biopsies prior to, at time of, or after cessation of thioguanine treatment. The median time between the first and second biopsy was 25 months (range: 14–54). Except for one normal liver specimen, any degree of irregularities including inflammation, steatosis, fibrosis and some vascular disturbances were observed in the biopsies. The rates of perisinusoidal fibrosis (91%), sinusoidal dilatation (68%) and nodularity (18%) were the same in the first and second liver biopsies. A trend towards statistical significance was observed for phlebosclerosis (36% of the first vs. 68% of the second biopsies, p = .092). Presence of histopathological liver abnormalities was not associated with clinical outcomes. Furthermore, two patients in this cohort had portal hypertension in presence of phlebosclerosis. In another two patients, nodularity of the liver resolved upon thioguanine withdrawal. Conclusion: Vascular abnormalities of the liver were commonly observed in thioguanine treated IBD patients, although these were not progressive and remained of limited clinical relevance over time.

Contains fulltext : 215423.pdf (Publisher’s version ) (Open Access) Emerging evidence exists that an altered gut microbiota is a key factor in the pathophysiology of a variety of diseases. Consequently, microbiota-targeted interventions, including administration of probiotics, have increasingly been evaluated. Mechanisms on how probiotics contribute to homeostasis or reverse (effects of) dysbiosis remain yet to be elucidated. In the current study, we assessed the effects of daily Lactobacillus casei strain Shirota (LcS) ingestion in healthy children aged from 12-18 years on gut microbiota compositional diversity and stability. Results were compared to healthy children without LcS exposure. For a period of 6 weeks, fecal samples were collected weekly by both groups. In total, 18 children were included (6 probiotics; 12 non-probiotics). At 1-week intervals, no differences in diversity and stability were observed in children exposed to LcS versus controls. LcS ingestion by healthy children does not result in a more diverse and stable gut microbiota composition. Large double-blind placebo-controlled randomized clinical trials in children should be performed to gain more insight on potential beneficial health consequences.